Studies in people and animal models suggest that depression is influenced by natural, fluctuations in the levels of 17β-oestradiol (E 2 ), as well as administration of E 2 -based therapies, such as selective oestrogen receptor modulators (SERMs). Elucidating the effects and mechanisms of E 2 is important to improve future E 2 -based therapeutics. An important question is whether effects of E 2 or SERMs for mood regulation act at the α or β isoform of the oestrogen receptor (ER) because some of the unwanted trophic effects of E 2 -based therapies may involve actions at ERα, rather than ERβ. In the present study, whether there are sex differences in depression-like behaviour of adult mice (experiment 1), and the effects of natural fluctuations in E 2 (experiment 2), or administration of E 2 or a SERM that has higher affinity for ERβ than for ERα (diarylpropionitrile; DPN) to ovariectomised (experiment 3) wildtype and ERβ knockout (βERKO) mice were investigated. Results of this study supported our hypotheses that: there would be sex differences favouring males for depression-like behaviour and endogenous increases in, or exogenous administration of, E 2 or administration of an ERβ SERM would decrease depression-like behaviour in wildtype, but not βERKO, mice. In experiment 1, adult male mice spent less time immobile in the forced swim test (i.e., showed less depression-like behaviour) compared with female mice. In experiment 2, pro-oestrous (higher circulating E 2 levels), compared with dioestrous (lower circulating E 2 levels), mice had reduced immobility in the forced swim test; this
NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript effect was not observed in βERKO mice. In experiment 3, administration of E 2 or DPN to ovariectomised wildtype, but not βERKO, mice decreased immobility compared with vehicle administration, these data suggest that ERβ may be required for some of the anti-depressant-like effects of E 2 .
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